Lithium Hexamethyldisilazide → (R)-3-((S,E)-2-(4-fluoro-3,5-dimethylbenzyl)-8-methylnon-6-enoyl)-4-benzyloxazolidin-2-one

HRID 1158129ノート

反応式

HRID 1158129 の反応式
[CH3:1][CH:2]([CH3:24])/[CH:3]=[CH:4]/[CH2:5][CH2:6][CH2:7][CH2:8][C:9]([N:11]1[C@H:15]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:14][O:13][C:12]1=[O:23])=[O:10].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[CH3:35][C:36]1[CH:37]=[C:38]([CH:41]=[C:42]([CH3:45])[C:43]=1[F:44])[CH2:39]Br>C1COCC1>[F:44][C:43]1[C:36]([CH3:35])=[CH:37][C:38]([CH2:39][C@H:8]([CH2:7][CH2:6][CH2:5]/[CH:4]=[CH:3]/[CH:2]([CH3:24])[CH3:1])[C:9]([N:11]2[C@H:15]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:14][O:13][C:12]2=[O:23])=[O:10])=[CH:41][C:42]=1[CH3:45]

参加物

5

反応物 3

HCID 2733832Lithium HexamethyldisilazideHCID 177507135-(Bromomethyl)-2-fluoro-1,3-dimethylbenzeneHCID 59512586(R)-3-((E)-8-methylnon-6-enoyl)-4-benzyloxazolidin-2-one

生成物 1

HCID 59512601(R)-3-((S,E)-2-(4-fluoro-3,5-dimethylbenzyl)-8-methylnon-6-enoyl)-4-benzyloxazolidin-2-one収率 68.1%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

To a cooled (−78° C.) solution of (R)-3-((E)-8-methylnon-6-enoyl)-4-benzyloxazolidin-2-one (2.000 g, 6.071 mmol) in 40 mL of THF, was added LiHMDS (9.1 mL, 9.1 mmol, 1.0 M in THF). The resulting mixture was stirred at −78° C. under N2 for 1 h and then a solution of 3,5-dimethyl-4-fluorobenzyl bromide (1.450 g, 6.678 mmol) in 10 mL of THF was added. After being stirred at −78° C. for 1 h the reaction mixture was warmed to room temperature for 2 h, and then quenched with 80 mL of NH4Cl solution and extracted with dichloromethane (60 mL×3). The combined organic extracts were dried (Na2SO4), filtered, and concentrated under reduced pressure. The product was isolated by Flash column chromatography (silica gel column) eluting with 0-100% dichloromethane/hexanes to give the title compound as colorless oil (1.925 g, 68% yield). GC-MS: tR=8.8 min; m/z 465 (M+).

後処理

  1. stirringAfter being stirred at −78° C. for 1 h the reaction mixture
  2. temperaturewas warmed to room temperature for 2 h
  3. customquenched with 80 mL of NH4Cl solution
  4. extractionextracted with dichloromethane (60 mL×3)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe product was isolated by Flash column chromatography (silica gel column)
  9. washeluting with 0-100% dichloromethane/hexanes

出典と根拠

ORDレコード
ord-7d22810b2f6c470ebba722897d8a8e1e
出典データセット
uspto-grants-2010_10
特許番号
US07807720B2

反応ノート

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